In this project, the unusual phenotype of a mouse line lacking two gap junction genes coding for the proteins connexin37 and connexin40 (Cx37 and Cx40) will be studied. These animals show altered vascular permeabilities in several regions of the body in addition to aberrant vasculogenesis in several organs. As the animals die perinatally, the project will also involve the generation of a conditional knockout animal carrying a deletion of the Cx37 gene and a conditional floxed Cx40 gene that can be removed postnatally by induction of the bacterial cre-recombinase gene using an inducible system. These animals will permit the dissection of aberrant vasculogenesis from endothelial dysfunction in adult blood vessels. Vascular structure will be studied using vascular casts comparing knockout and wild-type animals and conventional light and electron microscopy. Vascular function will be studied using injection of tracers into the vascular system of various sizes and demonstrating the locations of leakage of the tracers from the blood compartment into the surrounding connective tissues throughout the body.